GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293764/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293764GEOGSEfalseDecrypting Oncogenic Circuitry Through Translocation-Induced Enhancer Hijacking by TransFinder [Hi-C]While IGH enhancer translocations are well-established drivers of multiple myeloma (MM), routine diagnostics detect these events in only 32~38% of patients. Here we introduce TransFinder, a multi-omics pipeline integrating SMRT-seq, Hi-C, RNA-seq, and CUT&Tag to systematically resolve cryptic translocations and their hijacked oncogenes by deconvoluting enhancer-promoter neo-loops at rearrangement breakpoints. Applied to MM, TransFinder identified that t(16;22)(q23;q11), a canonical translocation known to activate MAF, also hijacks enhancers to activate RAB36. It further uncovered previously unrecognized translocations, t(5;8)(q35;q24) and t(1;22)(q25;q13), that activate MYC and CBX7 transcription, respectively, through chromatin topology rewiring. CRISPR-Cas9-engineered t(1;22)(q25;q13) recapitulated CBX7 induction, and pharmacological inhibition of CBX7 suppressed myeloma cell proliferation. Beyond MM, TransFinder identified enhancer-hijacking events in other malignancies, including chronic myeloid leukemia (CML), where t(9;22)(q34;q11) repositioned an enhancer to activate BCR-ABL1 transcription, and pancreatic ductal adenocarcinoma (PDAC), where t(2;12)(p24;q24) hijacked an enhancer to ectopically activate SDC1. By bridging 3D genome architecture with oncogene activation, TransFinder decodes oncogenic structural variants and their trans-activities, establishing clinically actionable dependencies of non-coding drivers in malignancies with complex karyotypic alterations.2026/09/03GSE293764GSM8889678GSM8889677GSM8889679GSM8889674GSM8889673GSM8889676GSM8889675GSM8889672GSM888967129480293764Homo sapiens